No decrease in preterm birth with n-3 fatty acid supplements

Long-chain n-3 fatty acid supplements do not appear to either decrease the risk of preterm delivery or increase the risk of late term delivery, according to data published in the New England Journal of Medicine.

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Maria Makrides, PhD, of the South Australian Health and Medical Research Institute, North Adelaide, and coauthors wrote there is evidence that n-3 long-chain polyunsaturated fatty acids play an essential role in labor initiation.

“Typical Western diets are relatively low in n-3 long-chain polyunsaturated fatty acids, which leads to a predominance of 2-series prostaglandin substrate in the fetoplacental unit and potentially confers a predisposition to preterm delivery,” they wrote, adding that epidemiologic studies have suggested associations between lower fish consumption in pregnancy and a higher rate of preterm delivery.

In a multicenter, double-blind trial, 5,517 women were randomized to either a daily fish oil supplement containing 900 mg of n-3 long-chain polyunsaturated fatty acids or vegetable oil capsules, from before 20 weeks’ gestation until 34 weeks’ gestation or delivery.

Among the 5,486 pregnancies included in the final analysis, there were no differences between the intervention and control groups in the primary outcome of early preterm delivery, which occurred in 2.2% of pregnancies in the n-3 fatty acid group and 2% of the control group (P = 0.5).

The study also saw no significant differences between the two groups in other outcomes such as the rates of preterm delivery, preterm spontaneous labor, postterm induction, or gestational age at delivery. Similarly, there were no apparent effects of supplementation on maternal and neonatal outcomes including low birth weight, admission to neonatal intensive care, gestational diabetes, postpartum hemorrhage, or preeclampsia.

The analysis did suggest a greater incidence of infants born very large for gestational age – with a birth weight above the 97th percentile – among women in the fatty acid supplement group, but this did not correspond to an increased rate of interventions such as cesarean section or postterm induction.

The authors commented that their finding of more very-large-for-gestational-age babies added to the debate about whether n-3 long-chain polyunsaturated fatty acid supplementation did have a direct impact on fetal growth, although they also noted that it could be a chance finding.

There were also no significant differences between the two groups in serious adverse events, including miscarriage.

The authors noted that the baseline level of n-3 long-chain polyunsaturated fatty acids in the women enrolled in trial may have been higher than in previous studies.

The study was supported by the Australian National Health and Medical Research Council and the Thyne Reid Foundation, with in-kind support from Croda UK and Efamol/Wassen UK. Two authors declared advisory board fees from private industry, and one also declared a patent relating to fatty acids in research. No other conflicts of interest were declared.